Showing 1–8 of 8 results for author: Ajdari, A

Bi-level Multi-criteria Optimization for Risk-informed Radiotherapy

Authors: Mara Schubert, Katrin Teichert, Zhongxing Liao, Thomas Bortfeld, Ali Ajdari

Abstract: In radiation therapy (RT) treatment planning, multi-criteria optimization (MCO) supports efficient plan selection but is usually solved for population-based dosimetric criteria and ignores patient-specific biological risk, potentially compromising outcomes in high-risk patients. We propose risk-guided MCO, a one-shot method that embeds a clinical risk model into conventional MCO, enabling interact… ▽ More In radiation therapy (RT) treatment planning, multi-criteria optimization (MCO) supports efficient plan selection but is usually solved for population-based dosimetric criteria and ignores patient-specific biological risk, potentially compromising outcomes in high-risk patients. We propose risk-guided MCO, a one-shot method that embeds a clinical risk model into conventional MCO, enabling interactive navigation between dosimetric and biological endpoints. The proposed algorithm uses a special order relation to fuse the classical MCO sandwiching algorithm with bi-level optimization, restricting the Pareto set to plans that achieve improvement in the secondary risk objective for user-defined, acceptable loss in primary clinical objectives. Thus, risk-guided MCO generates risk-optimized counterparts of clinical plans in a single run rather than by sequential or lexicographic planning. To assess the performance, we retrospectively analyzed 19 lung cancer patients treated with RT. The endpoint was the risk of grade 2+ radiation pneumonitis (RP), modeled using bootstrapped stepwise logistics regression with interaction terms, including baseline lung function, smoking history, and dosimetric factors. The risk-guided plans yielded a mean reduction of 8.0% in total lung V20 and 9.5% in right lung V5, translating into an average RP risk reduction of 7.7% (range=0.3%-20.1%), with small changes in target coverage (mean -1.2 D98[%] for CTV) and modest increase in heart dose (mean +1.74 Gy). This study presents the first proof-of-concept for integrating biological risk models directly within multi-criteria RT planning, enabling an interactive balance between established population-wide dose protocols and individualized outcome prediction. Our results demonstrate that the risk-informed MCO can reduce the risk of RP while maintaining target coverage. △ Less

Submitted 8 January, 2026; originally announced January 2026.

Ising energy model for the stochastic prediction of tumor islets

Authors: Lucas Amoudruz, Gregory Buti, Luciano Rivetti, Ali Ajdari, Gregory Sharp, Petros Koumoutsakos, Simon Spohn, Anca L Grosu, Thomas Bortfeld

Abstract: A major challenge in diagnosing and treating cancer is the infiltrative growth of tumors into surrounding tissues. This microscopic spread of the disease is invisible on most diagnostic imaging modalities and can often only be detected histologically in biopsies. The purpose of this paper is to develop a physically based model of tumor spread that captures the histologically observed behavior… ▽ More A major challenge in diagnosing and treating cancer is the infiltrative growth of tumors into surrounding tissues. This microscopic spread of the disease is invisible on most diagnostic imaging modalities and can often only be detected histologically in biopsies. The purpose of this paper is to develop a physically based model of tumor spread that captures the histologically observed behavior in terms of seeding small tumor islets in prostate cancer. The model is based on three elementary events: a tumor cell can move, duplicate, or die. The propensity of each event is given by an Ising-like Hamiltonian that captures correlations between neighboring cells. The model parameters were fitted to clinical data obtained from surgical specimens taken from 23 prostate cancer patients. The results demonstrate that this straightforward physical model effectively describes the distribution of the size and the number of tumor islets in prostate cancer. The simulated tumor islets exhibit a regular, approximately spherical shape, correctly mimicking the shapes observed in histology. This is due to the Ising interaction term between neighboring cells acting as a surface tension that gives rise to regularly shaped islets. The model addresses the important clinical need of calculating the probability of tumor involvement in specific sub-volumes of the prostate, which is required for radiation treatment planning and other applications. △ Less

Submitted 15 September, 2025; v1 submitted 28 August, 2025; originally announced August 2025.

Adjustable robust treatment-length optimization in radiation therapy

Authors: Stefan C. M. ten Eikelder, Ali Ajdari, Thomas Bortfeld, Dick den Hertog

Abstract: Traditionally, optimization of radiation therapy (RT) treatment plans has been done before the initiation of RT course, using population-wide estimates for patients' response to therapy. However, recent technological advancements have enabled monitoring individual patient response during the RT course, in the form of biomarkers. Although biomarker data remains subject to substantial uncertainties,… ▽ More Traditionally, optimization of radiation therapy (RT) treatment plans has been done before the initiation of RT course, using population-wide estimates for patients' response to therapy. However, recent technological advancements have enabled monitoring individual patient response during the RT course, in the form of biomarkers. Although biomarker data remains subject to substantial uncertainties, information extracted from this data may allow the RT plan to be adapted in a biologically informative way. We present a mathematical framework that optimally adapts the treatment-length of an RT plan based on the acquired mid-treatment biomarker information, while accounting for the inexact nature of this information. We formulate the adaptive treatment-length optimization problem as a 2-stage problem, wherein the information about the model parameters gathered during the first stage influences the decisions in the second stage. Using Adjustable Robust Optimization (ARO) techniques we derive explicit optimal decision rules for the stage-2 decisions and solve the optimization problem. The problem allows for multiple worst-case optimal solutions. To discriminate between these, we introduce the concept of Pareto Adjustable Robustly Optimal (PARO) solutions. In numerical experiments using lung cancer patient data, the ARO method is benchmarked against several other static and adaptive methods. In case of exact biomarker information, there is sufficient space to adapt, and numerical results show that taking into account both robustness and adaptability is not necessary. In case of inexact biomarker information, accounting for adaptability and inexactness of biomarker information is particularly beneficial when robustness (w.r.t. organ-at-risk (OAR) constraint violations) is of high importance. If minor OAR violations are allowed, a nominal folding horizon approach is a good performing alternative. △ Less

Submitted 12 February, 2021; v1 submitted 28 June, 2019; originally announced June 2019.

Comments: Revised manuscript. 44 pages, 13 figures

Towards an understanding of induced-charge electrokinetics at large applied voltages in concentrated solutions

Authors: Martin Z. Bazant, Mustafa Sabri Kilic, Brian D. Storey, Armand Ajdari

Abstract: The venerable theory of electrokinetic phenomena rests on the hypothesis of a dilute solution of point-like ions near a weakly charged surface, whose potential relative to the bulk is of order the thermal voltage ($kT/e \approx 25$ mV at room temperature). In nonlinear electrokinetic phenomena, such as AC or induced-charge electro-osmosis (ACEO, ICEO) and induced-charge electrophoresis (ICEP), s… ▽ More The venerable theory of electrokinetic phenomena rests on the hypothesis of a dilute solution of point-like ions near a weakly charged surface, whose potential relative to the bulk is of order the thermal voltage ($kT/e \approx 25$ mV at room temperature). In nonlinear electrokinetic phenomena, such as AC or induced-charge electro-osmosis (ACEO, ICEO) and induced-charge electrophoresis (ICEP), several Volts $\approx 100 kT/e$ are applied to polarizable surfaces in microscopic geometries, and the resulting electric fields and induced surface charges are large enough to violate the assumptions of the classical theory. In this article, we review the literature, highlight discrepancies between theory and experiment, introduce possible modifications of the theory, and analyze their consequences. We argue that, in response to a large applied voltage, the "compact layer" and "shear plane" effectively advance into the liquid, due to the crowding of counter-ions. Using simple continuum models, we predict two general trends, each enhanced by dielectric response: (i) ionic crowding against a blocking surface expands the diffuse double layer and thus decreases its differential capacitance, and (ii) a charge-induced viscosity increase near the surface reduces the electro-osmotic mobility. The first effect is able to predict high-frequency flow reversal in ACEO pumps, while the second may explain the decay of ICEO flow with increasing salt concentration. Through examples, such as ICEP of an uncharged metal sphere in an asymmetric electrolyte, we show that ICEO flows are ion-specific. Similar issues arise in nanofluidics (due to confinement) and ionic liquids (due to the lack of solvent), so the paper concludes with a general framework of modified electrokinetic equations for finite-sized ions. △ Less

Submitted 29 September, 2009; v1 submitted 26 March, 2009; originally announced March 2009.

Comments: Review with original material, expanded v2: 83 pages, 24 figs, 345 refs

Droplet traffic in microfluidic networks: A simple model for understanding and designing

Authors: M. Schindler, A. Ajdari

Abstract: We propose a simple model to analyze the traffic of droplets in microfluidic ``dual networks''. Such functional networks which consist of two types of channels, namely those accessible or forbidden to droplets, often display a complex behavior characteristic of dynamical systems. By focusing on three recently proposed configurations, we offer an explanation for their remarkable behavior. Additio… ▽ More We propose a simple model to analyze the traffic of droplets in microfluidic ``dual networks''. Such functional networks which consist of two types of channels, namely those accessible or forbidden to droplets, often display a complex behavior characteristic of dynamical systems. By focusing on three recently proposed configurations, we offer an explanation for their remarkable behavior. Additionally, the model allows us to predict the behavior in different parameter regimes. A verification will clarify fundamental issues, such as the network symmetry, the role of the driving conditions, and of the occurrence of reversible behavior. The model lends itself to a fast numerical implementation, thus can help designing devices, identifying parameter windows where the behavior is sufficiently robust for a devices to be practically useful, and exploring new functionalities. △ Less

Submitted 20 December, 2007; originally announced December 2007.

Comments: accepted for publication in PRL

Journal ref: Phys. Rev. Lett. 100, 044501 (2008)

Steric effects in the dynamics of electrolytes at large applied voltages: II. Modified Poisson-Nernst-Planck equations

Authors: Mustafa Sabri Kilic, Martin Z. Bazant, Armand Ajdari

Abstract: In situations involving large potentials or surface charges, the Poisson Boltzman(PB) equation has shortcomings because it neglects ion-ion interactions and steric effects. This has been widely recognized by the electrochemistry community, leading to the development of various alternative models resulting in different sets "modified PB equations", which have had at least qualitative success in p… ▽ More In situations involving large potentials or surface charges, the Poisson Boltzman(PB) equation has shortcomings because it neglects ion-ion interactions and steric effects. This has been widely recognized by the electrochemistry community, leading to the development of various alternative models resulting in different sets "modified PB equations", which have had at least qualitative success in predicting equilibrium ion distributions. On the other hand, the literature is scarce in terms of descriptions of concentration dynamics in these regimes. Here, adapting strategies developed to modify the PB equation, we propose a simple modification of the widely used Poisson-Nernst-Planck (PNP) equations for ionic transport, which at least qualitatively accounts for steric effects. We analyze numerical solutions of these MPNP equations on the model problem of the charging of a simple electrolyte cell, and compare the outcome to that of the standard PNP equations. Finally, we repeat the asymptotic analysis of Bazant, Thornton, and Ajdari(2004} for this new system of equations to further document the interest and limits of validity of the simpler equivalent electrical circuit models introduced in Part I for such problems. △ Less

Submitted 23 November, 2006; originally announced November 2006.

Steric effects in the dynamics of electrolytes at large applied voltages: I. Double-layer charging

Authors: Mustafa Sabri Kilic, Martin Z. Bazant, Armand Ajdari

Abstract: The classical Poisson-Boltzmann (PB) theory of electrolytes assumes a dilute solution of point charges with mean-field electrostatic forces. Even for very dilute solutions, however, it predicts absurdly large ion concentrations (exceeding close packing) for surface potentials of only a few tenths of a volt, which are often exceeded, e.g. in microfluidic pumps and electrochemical sensors. Since t… ▽ More The classical Poisson-Boltzmann (PB) theory of electrolytes assumes a dilute solution of point charges with mean-field electrostatic forces. Even for very dilute solutions, however, it predicts absurdly large ion concentrations (exceeding close packing) for surface potentials of only a few tenths of a volt, which are often exceeded, e.g. in microfluidic pumps and electrochemical sensors. Since the 1950s, several modifications of the PB equation have been proposed to account for the finite size of ions in equilibrium, but in this two-part series, we consider steric effects on diffuse charge dynamics (in the absence of electro-osmotic flow). In this first part, we review the literature and analyze two simple models for the charging of a thin double layer, which must form a condensed layer of close-packed ions near the surface at high voltage. A surprising prediction is that the differential capacitance typically varies non-monotonically with the applied voltage, and thus so does the response time of an electrolytic system. In PB theory, the capacitance blows up exponentially with voltage, but steric effects actually cause it to decrease above a threshold voltage where ions become crowded near the surface. Other nonlinear effects in PB theory are also strongly suppressed by steric effects: The net salt adsorption by the double layers in response to the applied voltage is greatly reduced, and so is the tangential "surface conduction" in the diffuse layer, to the point that it can often be neglected compared to bulk conduction (small Dukhin number). △ Less

Submitted 2 November, 2006; originally announced November 2006.

Energy Transduction of Isothermal Ratchets: Generic Aspects and Specific Examples Close to and Far from Equilibrium

Authors: Andrea Parmeggiani, Frank Jülicher, Armand Ajdari, Jacques Prost

Abstract: We study the energetics of isothermal ratchets which are driven by a chemical reaction between two states and operate in contact with a single heat bath of constant temperature. We discuss generic aspects of energy transduction such as Onsager relations in the linear response regime as well as the efficiency and dissipation close to and far from equilibrium. In the linear response regime where t… ▽ More We study the energetics of isothermal ratchets which are driven by a chemical reaction between two states and operate in contact with a single heat bath of constant temperature. We discuss generic aspects of energy transduction such as Onsager relations in the linear response regime as well as the efficiency and dissipation close to and far from equilibrium. In the linear response regime where the system operates reversibly the efficiency is in general nonzero. Studying the properties for specific examples of energy landscapes and transitions, we observe in the linear response regime that the efficiency can have a maximum as a function of temperature. Far from equilibrium in the fully irreversible regime, we find a maximum of the efficiency with values larger than in the linear regime for an optimal choice of the chemical driving force. We show that corresponding efficiencies can be of the order of 50%. A simple analytic argument allows us to estimate the efficiency in this irreversible regime for small external forces. △ Less

Submitted 12 April, 1999; originally announced April 1999.

Comments: 16 pages, 10 figures

Journal ref: Phys. Rev. E 60, 2127 (1999)